The development of systems for the production of human monoclonal antibodies has been considerably slower than the development of murine systems. In 1964 the first reports of the ability to propagate human lymphoid cell lines appeared (Pulvertaft (1964) The Lancet i, 238, 1064). Shortly after that Kamei and Moor (Kamei et al. (1968) Experientia 24, 410) demonstrated the induction of antibody synthesis by one of these cell lines (P3J) following antigenic stimulation in vitro. Attempts to confirm their work were unsuccessful (Krueger et al. (1974) J. Immunol. 112, 1415). More recent attempts to first select for B lymphocytes based on specific antigen recognition followed by their `immortalization` by EBV transformation has led to the establishment of B lymphoid cell lines which synthesize specific antibodies (Steinitz et al. Nature (London 1977) 269, 420). Fusion of mouse myeloma cells with human immunocytes resulted in the production of hybrids synthesizing human immunoglobulins (Schwaber et al. Nature (London 1973), 244, 444). Application of this method to mouse lymphocytes led to the development of mouse monoclonal antibodies (Kohler et al. Nature (London 1975) 256, 495). In contrast, human antibody production by mouse-human hybrids was unstable. To overcome this instability, a human B lymphoid cell line (Croce et al. Nature (London 1980) 288, 488) and a human myeloma cell line (Ollson et al. (1980) P.N.A.S. U.S.A. 77, 5429) have been utilized as fusing partners for human immunocytes. While all of these systems have been employed with some success none has been demonstrated to work reliably enough to be generally accepted. Fougere et al. P.N.A.S. U.S.A. (1972) 69, 330 and Davidson P.N.A.S. U.S.A. (1972) 69, 951 showed that expression of differentiated properties in hybrid cells may depend on gene dosage. This or an operationally similar phenomenon was successfully applied to the construction of a non-producing mouse myeloma cell line (Shulman et al. Nature (London 1978) 276, 269).